Hormone replacement therapy (HRT)

Hormone Replacement Therapy (HRT)—also known as Menopause Hormone Therapy (MHT)—involves the administration of estrogens (and, where appropriate, progestogens) to alleviate symptoms resulting from decreased ovarian hormone production in menopause. In select cases, low-dose testosterone may also be considered.

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1. Goals & Indications

• Relief of vasomotor symptoms: hot flushes, night sweats, sleep disturbances, mood swings

• Treatment of vulvovaginal atrophy: dryness, dyspareunia, urinary urgency, recurrent cystitis

• Prevention of osteoporosis and fractures in women under 60 or within 10 years of menopause onset

• Women with premature or early menopause (<45 years) often benefit long term to reduce cardiovascular, bone and mood risks

• Considered even in cancer survivors under specialist assessment when symptom burden is high

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2. Timing & Patient Selection

• Initiating HRT before 60 years of age or within 10 years of menopause provides the most favorable benefit-to-risk ratio

• Starting after age 60 or more than 10 years post-menopause increases risk of stroke, venous thromboembolism (VTE), and breast cancer, with less benefit

• Both age and personal/family health history guide decision-making

• In women over 65, retrospective data suggest benefits may persist with individualized use

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3. Routes & Formulations

• Systemic Estrogen:

  • Oral pills (estradiol or conjugated estrogens)

  • Transdermal (patch, gel, spray): lower risk of VTE and stroke, preferred for women with thrombosis risk

• Local Vaginal Estrogen:

  • Creams, tablets, rings for isolated urogenital symptoms; minimal systemic absorption

• Progestogen (if uterus intact):

  • Continuous or sequential regimens protect against endometrial hyperplasia

  • Micronized progesterone or progestogen-releasing IUD may carry lower breast cancer risk than synthetic forms

• Testosterone (off-label):

  • Low-dose transdermal may improve libido and energy; use under specialist supervision

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4. Benefits

• Highly effective in reducing vasomotor and urogenital symptoms

• Improves sleep quality, mood, and overall quality of life

• Protects bone density and reduces fracture risk

• Early initiation may confer cardiovascular benefits, improve lipids and insulin sensitivity

• May reduce diabetes incidence in perimenopausal women

• Observational and emerging data suggest no reduction in life expectancy over appropriate durations

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5. Risks & Safety Considerations

Thromboembolic and Cardiovascular Risks

• Oral estrogen increases VTE risk (~2‑3× higher), especially in older women or those with obesity or previous clots

• Transdermal estradiol appears to not increase VTE risk, even in women with prior thrombosis

Stroke and Cardiovascular Events

• Oral forms carry a small increased risk of ischemic stroke; transdermal minimized risk

• Starting therapy in women aged 60+ is more strongly associated with cardiovascular harm

Breast and Gynecologic Cancer

• Combined estrogen–progestogen therapy modestly increases breast cancer risk, especially after 4–5+ years

• Estrogen-only therapy (in women without a uterus) carries ≤ baseline breast cancer risk

• Unopposed estrogen in women with a uterus increases endometrial cancer; progestogen mitigates this risk

• Slight increase in ovarian cancer risk (~1 additional case per 2,500 women over 5 years)

Gallbladder Disease

• Estrogen therapy increases gallstone risk and gallbladder surgery rates

Other Effects

• Fluid retention, breast tenderness, bloating, mild weight gain, irregular bleeding—usually transient

• Cognitive neutral for most women; benefit uncertain if started after a decade post-menopause

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6. Clinical Guidelines & Recommendations

• Primary-line therapy for moderate to severe menopause symptoms per NICE updated guidance

• Combined therapy advised only if uterus intact; local vaginal estrogen for isolated urogenital symptoms

• Women with early menopause strongly recommended to remain on HRT until average menopause age (~51)

• GP-based decision-support tools (e.g., MENO.Pause) now available to individualize analysis, even for cancer survivors or high-risk patients

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7. Prescription & Monitoring

• Use the lowest effective dose for symptom control

• Systemic estrogen dosing tapered once symptoms resolve; annual review recommended

• Regular follow-up includes:

  • Breast screening according to local protocols

  • Blood pressure, weight and metabolic assessment

  • Consider bone density testing for fracture risk

• Reassess benefit-risk balance at least annually

• Discontinuation or taper considers symptom recurrence and patient preference

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8. Special Populations

• Early menopause (premature ovarian insufficiency): HRT is recommended until at least age 51–52

• Women with a history of hormone-sensitive cancer: individualized decision-making by specialists; some survivors may safely use HRT when benefits outweigh risks

• Women with VTE history or thrombophilia: transdermal estrogen preferred; risk stratification critical

• Perimenopausal women (<50 years) with bothersome symptoms may benefit, especially if not using contraceptives

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